This research proposal is designed to investigate the factors involved in cell death and cytodifferentiation during morphogenesis by using the isthmo-optic nucleus of the avian brain as a model. The role of afferent input on cell death and cytodifferentiation will be analyzed by electron microscopy. The nucleus will be deprived of its afferent synaptic input by placing lesions in the optic tectum of duck embryos on the fifth day of incubation. By using this type of approach it will be possible to determine 1) Whether cell death is due to lack of afferent stimulus, and 2) The point to which cells can differentiate on their own (i.e., when they become dependent on afferent stimulation for further differentiation and subsequent survival). Tectal lesions, using cautery, will also be placed at later stages of development when the cells of the nucleus have received afferent stimulation in the form of synapses, to investigate whether cell survival depends on a continuous supply of afferent stimulation, or whether an initial stimulation is adequate to guarantee survival by electron microscopy. The role in increased peripheral field of innervation on the corresponding decrease of cell death (or corresponding increase in cell survival) will be investigated by transplanting an additional eye which will double the peripheral field of innervation (retina) of the nucleus. Autoradiography will be utilized to demonstrate continuity of the transplanted eye with the optic tectum. Cell counts of the nucleus by using camera lucida will be made to determine an increase in the number of surviving cells. Dying cells will be examined by employing electron microscopy.